title: Analysis of erectile responses to imatinib in the rat.
abstract: OBJECTIVE
  To investigate the erectile and cardiovascular responses to the tyrosine kinase inhibitor imatinib in the rat.
  
  
  METHODS
  The effect of intracavernosal injection of imatinib on the intracavernosal pressure (ICP), ICP/mean arterial pressure (MAP) ratio, area under the curve, and duration of the increase in ICP and the effect of intravenous injection of imatinib on the MAP, cardiac output, and total peripheral resistance were investigated. The effect of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on the responses to imatinib was investigated.
  
  
  RESULTS
  Intracavernosal injection of imatinib produced significant dose-related increases in the ICP, ICP/MAP ratio, area under the curve, and duration of the increase in ICP and decreases in the MAP. The erectile responses to imatinib were rapid in onset and short in duration. The erectile responses to imatinib were not significantly altered by NG-nitro-L-arginine methyl ester or cavernosal nerve crush injury, and imatinib was significantly less potent than the nitric oxide donor sodium nitroprusside in inducing erection. Intravenous injection of imatinib produced significant dose-related decreases in the MAP without significantly changing the cardiac output, and imatinib was significantly less potent than sodium nitroprusside in decreasing the MAP. Systemic vascular resistance was decreased in a significant dose-related manner, and the vasodilator responses to imatinib were not altered by NG-nitro-L-arginine methyl ester.
  
  
  CONCLUSIONS
  The present results have indicated that imatinib has significant erectile and systemic vasodilator activity in the rat that is not dependent on nitric oxide release. Another tyrosine kinase inhibitor, nilotinib, also increased the ICP and decreased the MAP in the rat. These data suggest that tyrosine kinases might play a constitutive role in maintaining penile tumescence and the baseline vasoconstrictor tone in the peripheral vascular bed.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Pankey
authors.forename: George F
authors.initials: GF
authors.lastname: Lasker
authors.forename: Serap
authors.initials: S
authors.lastname: Gur
authors.forename: Wayne J G
authors.initials: WJ
authors.lastname: Hellstrom
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D062186:Arterial Pressure / Q000187:drug effects*; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000068877:Imatinib Mesylate; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000098:blood supply* / Q000294:innervation / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D009599:Nitroprusside; D009569:Nitric Oxide; D000068877:Imatinib Mesylate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester